Principal Investigator: R. Lane Smith, PhD Project Staff: Dennis R. Carter, PhD; Gary S. Beaupré, PhD; Derek P. Lindsey, MS; G. Sims, MD; AR Hoffman, MD; and D.J. Schurman, MD Project Category: Arthritis - 2001 Objective: This study will investigate how intermittent hydrostatic pressure applied over precisely defined loading periods serves as a stimulus for articular cartilage repair and regeneration. The experiments test effects of applying intermittent hydrostatic pressure on human osteoarthritic cartilage cells to: (1) induce expression of the large aggregating proteoglycans, aggrecans and type II collagen; (2) decrease expression of the matrix metalloproteinases; and (3) act in concert with the effects of serum-derived and purified growth factors. Research Plan: Intermittent hydrostatic pressure is an important determinant of the stress modes that occur with mechanical loading of normal diarthrodial joints during daily activity. The work proposed here addresses the hypothesis that activation of processes important for repair and regeneration of articular cartilage requires selective mechanical loading regimens to induce gene expression of critical cartilage matrix proteins. The specific hypotheses to be tested are that precisely controlled interval loading with variable high levels and varying frequencies of intermittent hydrostatic pressure will stimulate renewed expression of articular cartilage extracellular matrix macromolecules. The experiments will apply hydrostatic pressure to primary cultures of human articular chondrocytes and quantify the cellular response through extracellular matrix protein expression. Three experimental aims will test effects of interval loading using: (1) varying physiological levels (1, 5 and 10 MPa); and (2) frequencies (0.1, 1 and 10 Hz) of hydrostatic pressure on (a) aggrecan expression, and type II collagen expression (b) expression of cartilage degrading matrix metalloproteinases and (c) the interaction between hydrostatic pressure and cartilage stimulating insulin-like growth factor I and basic fibroblast growth factor. Work Accomplished: Three manuscripts are in preparation describing the effect of intermittent hydrostatic pressure on normal and osteoarthritic cartilage. Three abstracts were accepted for presentation at national meeting, two in 2001 and one in 2002. Funding Source: VA RR&D Merit Review Funding Status: Approved |
